CS252465B2 - Insecticide and acaricide - Google Patents

Abstract

A novel crystalline material consisting of a enantiomeric pair of cyhalothrin isomers in the form of the racemic mixture and having greater insecticidal activity than cyhalothrin itself is described, together with a process for obtaining the enantiomeric pair of isomers by crystallization from concentrated cyhalothrin solutions in lower alkanols or liquid alkanes.

Description

The present invention relates to an insecticidal composition.

Compound alpha-cyano-3-phenyloxy-benzene-cis-3- (Z-2-chloro-3,3,3-trifluoroprop-1-errl-yl) -2,2-dimethylcyclopropanecarbooylate, also known as cyhalothrin, preparation of this compound and its pooling as an insecticide is described, among others, in U.S. Patent No. 4,183,948. This product is a mixture of four isomers, which are described as follows:

Isomer A - ester derived from

Isomer B - an ester derived from (+) - cis -acid and alpha-SXalcoaol of (-) - cis -acid and α 1 β-α-R β- when the alcohol is present.

Isomer C ester derived from (+) - cis-acid and alpha- (R) -alkchl

Isomer D - ester derived from (-) - cis-acid and 11fl- (S) -alkacacle

CyУalo0.hrin alone normally contains from 40 to 60 wt. Isomers A and B and 60 to 40% by weight of isomers C and D and form a viscous liquid at room temperature. By cooling, crystallization cannot be induced in this mixture.

Isomer A and isomer B have identical physical characteristics, and their solubility. melting point and the like differ only in the directions in which they rotate the plane of the polarized light and, as such, repress the enantiomers. Similarly, isomer c and isomer D represent the second two enantiomers.

From the work of P. D. Beeniey i1. Pessic. Sci., 11 (2) 156-164 (1980), it is known that isomer A is the most harmful of the four isomers and that isomers B and D are non-salivary in fly tests (Musea dommetica). In this test, isomer A is in fact 25 times more active than the known insecticide permeehhin and is the most effective synthetic insecticide reported so far. While it would be desirable to use isomer A alone as the active ingredient of the insecticidal compositions, this is not readily accomplished for economic reasons. For this purpose, it would be desirable that portions of the isomeric moieties of both the acid and the alcohol be prepared by chiral synthesis and then reacted together in a manner that ensures that the chirality is not altered. These techniques have not yet been developed to the extent that the synthesis is carried out economically without the simultaneous production of undesirable isomeric products requiring separation under the influence of the second reagents.

It has now been found that a pair of enantiomers consisting of isomer A and isomer B can be readily separated from isomers C and isomers D in a physical manner not requiring chiral synthesis or chemical resolution and by which insecticidal products of acceptable efficacy can be prepared economically.

SUMMARY OF THE INVENTION The present invention relates to an insclicidal composition comprising, as an active ingredient, a mixture of the isomers of the alpha-3-Senoyye-benzyl cis-3- (2-chloro-3,3 _of 3-trilloorpropyl-esyl) -2,2- A mixture of at least 90% by weight of an enantiomeric pair of isomers represented by (S) -allaluminum-3-Snoxyesyl (1R (4)) -3- (Z-) is an active diluent or carrier. 2-Chloro-3,3,3-trifluoroprop-1-eel-yl) -2,2-dimethylcyclopropanil recylase and (R-alpha-kylnc-Sellcyyesnzy1 (1S, ccs) -3-- (Z-2-chloro) -3,3,3-trifluoropropyl-1-eel-yl) -2,2-trimethylcyclopropylpropyloyoylate and not more than 10% by weight of the other isomers of 11β-kylno-phenoyybenzyl cis- (2-chloro-3,3) 3-trifluoropropyl-1-esyl-2,2-dimetylcyclopropylcarbonyl acetate.

The active ingredient of the composition is prepared by:

(a) prepare a solution of cyhalotaril in an organic solvent selected from lower alkanols having at least 6 carbon atoms and liquid alkanes containing up to 8 carbon atoms,

b) the solution is cooled to from -20 ° C to + 1 ⁰ ° C and the case přidlá to a cooled solution mnnžsSví crystals inantiomerní pair of isomers to remain then in the solid undissolved state, the added crystals

(c) maintaining the solution at said temperature range for a sufficient period of time, and crystalline material precipitates out of solution; and

d) precipitated crystalline material. is separated from the solution and

e) optionally recrystallizing until substantially free of the other isomers of alpha-cyano-3-eroxyxybenzyl 3 '(2-β-β-3,3,3-triftutipijp-1-elil-yl) -2, -dioethylcyclitropanpanabab) tχlátu.

Substantially wear-free bonded mass means that the product contains no more than 10% by weight of any other cyhalothrin isomer.

Preferred alcoholic solvents are ethanol, isopropanoo, butamino-ol, butan-2-ol, peenol-1, iso-opano / t -butanol (1: 1), istprtpanite / 1, ethaneddol (2: 1). 1). A particularly preferred solvent is isopropanol. Preferred liquid alkane solvents are n-hexane and n-hexane.

Preferably, under the term 1: 5, preferably 1: 1 concentrated solution, is one that contains from 2: 1 to parts by weight of mono-cyhalotarial to solvent.

Cyyaaiohrin použžtý in this process may be contaminated with up to 10% amotnotSních t ^{d d} ppoí aaícíca trais-itooerů and (EJ-isomer. Cyhalothrii preferably at least 95% purity is used since this usually provides the Product in higher yield and purity.

If the process is carried out with the addition of a certain amount of crystals of the enantiomers of the isomers, then the time (Multitude of Inantiomeric Pairs of Isomers) is usually shortened by the quality of the cylinders. r vysok high pressure liquid pair of isomers separated from other direct χχ οθ ^).

required to precipitate the product from solution. sufficient for addition, can be obtained by chromaaography of the desired one

The process is preferably carried out by preparing a solution, possibly under slight zahhátí · ^p and ^k thaw ^ cools te ^p lot in the range of ^d 0 ^d 10 ° ^C at the initial ^d OBU during ^the ter ^é substantial onn0sSví product crystallized and then further cooling the solution to a temperature from ⁵ ° C -I ^d about ^-5 ° ^C at a portion druta ^d ^ ob ^ Oby not substantially complete it ^ ^ ace tal ^straight before collecting the precipitated product.

In order to separate the product from the other isomers which may precipitate with the product during crystallization, it is required to crystallize it, then it may be carried out in a suitable recrystallization solvent, for example in the solvent mentioned above as the pellet solvent in the process of the invention.

The product may be eliminated in one or two different forms, hereinafter referred to as "product I" and "product II". Typically, the product I is eliminated only slowly and the time required to achieve a sufficient yield is preferably at least 7 to 15 days or more. Product II is precipitated with ryclheli and a good yield can be obtained over a period of from 1 to 6 days.

Where crystals of the enantiomeric isomer of the isomers prepared by the high pressure liquid cartridge are added, the excretion is usually carried out in the form of product I.

This precipitated material is recrystallized several times and then more inoculated to inoculate further crystallites, then the likelihood of obtaining product II increases, although it may be necessary to perform a number of crystallizations before product II actually precipitates. Once product II is formed and it is used to inoculate further crystallizations, it always causes product to precipitate in the form of product II.

The product I precipitated in the above manner is a white crystalline material, m.p. 36-42 ° C. If it is freed from contamination of the remaining amounts of isomer C with isomer D by recrystallization, product I melts at 41 to 42 ° C. Infrared spectral analysis shows that it consists of a mixed crystal conglomeeate, wherein each individual crystal is composed of molecules of one isomer, either isomer A or isomer B, and that the crystal potential of each isomer is about the same. Product I is therefore a racemic mixture. These crystals are fine needles, which, as mentioned above, are slowly secreted from concentrated cyhalothrin solutions. Separation of the product by filtration is also slow due to the tendency of fine needles to plug the filter.

Product II is characterized by a melting point above 47 ° C, typically 48 to 50 ° C. This form crystallizes faster and the crystals are rhomboid in appearance, although in fact they are moonlit. This makes it easier to filter because the crystals of this mold do not tend to clog the filter like the needles of the mold described above.

Infrared spectroscopy and X-ray crystallographic analysis of the above melting form show that each individual crystal is composed of equal amounts of isomer A and isomer B arranged regularly in a crystal lattice. This form is thus a racemic compound.

Data relating to the crystalline form of product II was obtained by studying a chajaaltristil X-ray crystal action of dimensions of about 0.13 x 0.13 x 0.12 mm using a Philips PW 1100 four circle X-ray diffracSometer with Mo-K ^ radiation from of a graphio moshohome. Was použžt and ²⁰ stanovací ^PU with ^b s ^ rycř Ostia ^ nin ^ ^0, s 5 "\ stonovací S ^ a of 0.8 ° and reflections with 3 <0? 25 ° was studied using the technique described by KR Adam et al ., Inorg. Chem., 1980 19, 2 956. The data obtained for product II are summarized as follows: crystal-form: C2 / ca = 34.764 (5, & = 101.95 (3),

-3 density = ^1.343 g / cm ^, (Μο-Κ ^) = 1.77 cm ^-1 , b = 7.023 (2), c = 1.8 624

U = 444.846 nm Z = 8

F (000) = 1856.

(MoolKJ = 0.071.069 nm.

(3) nm

The crystal lattice consists of regularly arranged three-folded monococci of the two isomers A and B, each of which contains a tris-cormylglycine in trans configuration to the cyclopropane group via a double bond (Z-cleavage). The unit cell contains 4 &lt; 5 &gt; C (S) of each of the enantiomeric isomers.

The invention is further illustrated in the following examples.

In the examples, the isomer A is referred to herein as the 1R-cis-S-isomer, i.e., the isomer with R-co-configuration at the carbon atom of the cyclopropane ring attached to the carboxylate group, cis-arrangement refers to the relationship between two hydrogen atoms on the cyclopropane ring on a cyano-bearing carbon atom. Isomer B is referred to as the 1S, cis-R-isomer (mer, isomer C as the 1R, is-R-iocme, and isomer D as the 1S, cis-S-10 isomer.

Example 1

This example illustrates the separation of alpha-cyano-3-phenoxybenzyl cis-3- (2-2- [1,3], 3,3-trifluoropropyl-1-en-1-yl) -2,2-dimethylcylpropyl capanecarboxylate into pairs of enantiomeric isomer.

The material to be separated was characterized by chromatography on a thin layer at 0.25 mm (analytical purity) of agel forces using vigorous mixtures of solvents. The material was slightly subdivided into two components corresponding to two pairs of direct enantiomers. The relative Rf values for these two components were ice:

Elution agent Diethyl ether: n-hexane Rf (diameter) Á ^R _f 10:90 0.22 0,025 15:85, 0.28 0.030 20:80 0.33

Separation of this material was performed using high pressure liquid chromatography on a Waters Assooiates System 500 apparatus with a PrePAK-500 silitrgegovg column. The 0.5h cyhhaothrin batch sees a 55:45 mixture of the 1S, cis-S / 1R, cis-R: 1R, cis-S / 1S, cis-R enantiomers. J ^{as in e} l ^b protrudes yl ^and used a blend de-ylethyl-ru-ru and petrolet (TV ^40-60 ° C) mixture (1: 9) at a flow rate of 0.2 liters per minute. Fractions were collected after four recycling operations. The first fraction was identified by proton Maarneic resonance speetroscoopia. The 1R, cis-R / 1S, cis-S enantiomeric pair and the second fraction as the 1R cis-S / 1S, the cis-R enantiomeric pair. Each fraction had a purity of about 98% and together corresponded to about 60% of the quantified quantity. PMR data are summarized in the following table (beta values in CDDip:

1R, cis-S / 1S, cis-R 1S, cis-S / 1R, cis-R

l34 (s)

1,983

2.07

2.19 (m)

2.29

2 ^, 38 ⁰

2.29

2 ^, 38 ^J

6.38 (s)

6.32 (s)

6.773 l (d)

6.87J

6.97 to 7.50 (m)

6.773 (d)

6.87 J

6.97 to 7.50 (m)

Example 2

This example illustrates the crystallization of 1R, cis-S / SS, cSs-IgMRI pair from a cyhalotrin solution. The crystals used for seeding were prepared according to the procedure of Example 1.

455.6 g of a mixture of cis -s-isomers of alpha-cyano-3-renoxybrisyl 3- (Z-2-chloro-3,3,3-trichloro-propyl-1-enil-yl) -2,2-dimethyl-cyclopropyl-pancarboxylate containing 43.2 wt. % of the 1R, cis-S and 1R, cis-R isomers and 56.8 wt. The 1S, cis-S and 1R, cis-R isomers were dissolved in 460 ml of isopropanol, which had been previously dried by dessillation from calcium hydride. Dissolving was carried out by heating ^{with a} confidential ^and also ^to a 50 ° C. · Thawing ^of the cooled to 3 ° C while it MICL-coated magnet polytrtralžgrrtthyrirem. Then several crystals of the mixture are added. 1R, cis-S and 1R, cis-R isomers of alpha-cyano-3-renggybenzyl 3- (Z-2-chloro-3,3,3-trifluoropropyl-piperidin) -2,2-trimethylcyclopropanababyl-ethyl. Stirring was continued at this temperature for 9 days, then the suspension was cooled to -10 ° C and the mixture was vigorously stirred with a polytetrafluoroethane stirrer for 7 days.

The precipitated solid was filtered off at 3 ° C to dryness, washed once with 100 ml of petroleum ether ^40-60 ° C, ^cooling, from ^eného to ³ ° C and then dried ^d of ^the onstantní ^h mo ⁰ noo ^with and in a vacuum dessicator over kysličnkeeo iosfoeečným. 97.6 g of white crystals are obtained. This product contains 86.9% by weight of capillary gas chromototootaphia. sOss. 1: 1 R, ^cis-R-ate OA soooerů starting iálu. Solid ^p from ^F l rozpuutí in ³⁰⁰ ml ^b EFTA ^dé him 40-50 ° C petroleum ether-solution thereto ^under stirring cooled down to ³ ° C and as ^{a n} co is at ^d and Neko ^of i ^kk r ^y hundred ^profiles mixture ^of a 4S-S and 1S, cis-R isomers of the tert-phthalino-3-itnoxybenzyl 3- (Z-2-chloro-3,3,3-trifluoroprop ^- 1-ee-1-yl) -2,2-dimethyloyclo ^p roptnk ^and rboo ^y Uate. After 2 hours the resultant white suspension oddiltruje at ³ DEG ^{C. and} solid below about l ^{d d} e ^{d i} is the dryness. Further drying in the beam ^to exi over ator ^at Kyss ^No Nike iosfoeečným afforded 73.6 g of a white solid comprising! 92% hmco. SMMS lR, cis-S and 1S, cis-R isomers tlft-solubility-3-f1noxyУo1zyl Зз (from - 2C! Clore-3,3, ^3--tri.fluor prop-l-en-l-yl) -2,2ldíoethylcyklo ^p ro ^p ANK ^and tbooylátu, mp 36-42 ° C.

Example 3

A mixture of cyltltri isomers containing 6.4 g of the 1R, cis-S isomers, 6.4 g of the fS, cis-R isomers, 3.2 g of the 1S, cis-S isomers, and 3.2 g of the 1R, cis-R isomers rozpuusí in n-hexane (20 ml) and stirred ^{with in} and e ^ e ^ ^d OSF ^ears u ^p s tep ^ tO -5 ° C. ^p o dissolve ^it and cooling, ^p Rida někooik mLligamtó racemic mixture (obtained according to Example 2 and further compounding číšsěného crystallization temperature until counting ^{I J} e ^41.5 and ^42, 0 ° C. Stirring was continued ^{for p,} and ^ l is ⁶ hours ^p s - ⁵ ° C. the precipitated solid carboxylate ^l ^^ ^k from oestrus to -toovtn s ^{s s} s ^{to n s} LTN funnel laze ^ ^ to 0 ° C and twice ^for PA ^and LT PR ^ y is rejuvenated flock to ^-5 ° C. ^from iS ^to s ^ ^{t to 9.30} g and m ^ tt eiálu and ^{48 F 49.5} ° C ^{Purity y is} at least 99% relative to the isomers and contained cyhlαotlrinu ^^ Affairs at least 96.3% of the 1R, cis-S, and 1S-is-R-isomers in the same polymers.

This product is different from the prodrug according to Example 2, according to infrared red eye analysis. The crystalline form is also different (rhomthioid rather than acicular) and, together with a higher melting point, it is a racemic compound where individual crystals contain the same multitude. The cis-S and 1S, cis-S, R-10-mer, the OOS molecules are regularly arranged in a crystal lattice.

I-F spectrum (liquid paraffin suspension): 1,050, 1,030, 1,010, 990, 970 (inilex), 963, 950, 935, 920, 908, 904, 895, 888, 873, 838, 830 ( inilex), 820, 805, 795, 785, 760 ^, 74 ^8, 725 ^, 702 ^, 695 ^, 650 ^{cm -1} .

Figures 1 and 2 show the infrared spectra of the product of this example and of the product of Example 2. Figure 3 shows the i-fa and red spectra of the 1-, cis-S-ionotr alone. It can be seen that the spectrum of the product of Example 2 and the R, C, -Siimeter itself are identical, indicating that the product of Example 2 is a racemic mixture conglomerate, while the different spectrum of the product of Example 3 indicates that a racemic compound.

example ⁴

A mixture of cyhltotrin isomers containing 20.61 g of isomer A, 20.61 g of isomer B, 4.04 g of isomer C and 4.04 g of isomer D is dissolved in hot hexane (100 mL), cooled to 5 C and added ^with e. ^m ^ ^s ^^ for rnnn ^d uct ^at under-la lecture ^{du CART third The mixture is then E and} L ^at porn oohl ⁱⁿ ^ i t ^{t i} i n ^{it lo} rnícMní to ^-5 ° C.

The precipitate was filtered off, washed on the filter with cold hexane and air dried. T ^{yield and} the KTA rac ^ ^ ou ^ ni-on ^{and (2} 8.6. ^G), m. ^{P. 49-50} ° C

Example 5 ^T ent ^of comm d ^ v ^^ r ^ is Шп ^of znýc pouštěde ^h ^ r 1 ratio ^{in Solvent} Oust ^{sd EL} ^ h ^ othrio, ^{d and} y ° ^of Ю ^^ у ^above TSZ ^{e and} the quality of ^p roducts the ^f orm ^of racemictó ^ Ness ^(Pr ° ^d u ^c t i). The cysteine used as starting material contained 42% (+ 1%) of the 1R, cis-S / 1S, cis-R pair of isomers. In each experiment, several milligrams of the racemic mixture crystals were added after

Cool to desired temperature as seed for crystallization. The results are summarized in Table I.

W 'Example 1a d 6 ‘

This example illustrates the precipitation of the racemic compound of the product (Product II). A mixture of technical isotropin (200 g, 95.5% pure) and isopropanol (200 mL) is placed in a round glass flask containing a series of glass beads, cooled to -5 ° C and crystals of the racial compound are added. 4.0 g). The cooled mixture was stirred at -5 ° C for 23 hours while the flask was rotated. The precipitate was filtered ŠMÍD spillover into the suction sintoované · n ^k y ^and Lev ^BC e ^d c ^hl Azen ^s at ^- 5 ° C and ^ ltaačn :! ^{OL AC} washed it with comminuted ^{d BC} edchlazeným n-hexane (one volume Poodle) and is obtained from R ^ is-S- and S, ^ cií5R -somerů iyhaaotUrinš (after drying) the racemic compound sestávajcí ° (39.5 g), m.p.

C.

Ta table 1

Rooppoštědlo /

Attempt% Content

Hmmonpst

Mass

Temperature ° C /

C. ^ yhaothrin (G) volume (ml) time (days) precipitates (G) 1R, cis-S / 1S, cis-R isomeric pair 1 5.0 ethanol 5,0 3/8 0.26 84.3 2 10.0 n-propanol 10.0 3/11 1.03 86.7 3 50.0 n-propanol 50.0 3/12 and then -10/4 8.7 91.9 4 5.0 n-butanol 5.0 3/33 0.14 86.9 5 ' 5.0 sec-butanol 5.0 3/8 0.41 82.6 6 10.0 isobutanol 10.0 3/11 1.18 79.0 7 5.0 t-butanol / isopropanol (1: 1) 10.0 3/14 0.64 88.3 8 5.0 n-Pentanol 5.0 3/33 0.64 68.8 9 10.0 isopropanol 5.0 3/11 0.97 79.1 10 10.5 n-hexane 10.0 0/9 0.61 99.1 11 10.0 n-heptane 10.0 3/22 0.48 98.6 12 9.6 n-heptane 10.0 3/11 0.73 96.5 13 10.0 2,2, trim trimethyl- pentane 10.0 3/8 i, 17 80.3 14 2,000 · n-hexane 2000 0/18 then -5/7 , 406 93,3 ^X 15+ 200.0 isopropanol 200 0/7 26,5 ^XX 92.0 16+ 204.0 isopropanol 200 5/7 9,6 ^XX 97.0

x After crystallization from petroleum ether ⁽⁴⁰ to ⁶⁰ ° C), weight ² 81 ^g . xx Except for seed crystals + 4.0 g of added seed crystals

Claims (2)

SUBJECT OF THE INVENTION Ioteekicidium and acaicidium agent acting as the active ingredient of the cis-3- (2-cis-3-isomeric -3,3,3-α-β-β-1-βη-1-α-β-isomers) -2,2-dioeehhycyclo active ingredient - The propoxycarboxylate in a salt of agricultural and tartar with a suitable diluent or carrier, characterized in that it contains at least 90% by weight of the active ingredient. enanticoeroid pair of isomers of (S) -halo-3-phenoxybenzyl (1R, cis) -3- (Z-4-chloro-1,3,3-trifluoropropyl-1-en-1-yl) -2,2-Dioethylcyclohexanopropoxylate and (R) -layayyanc-3-phonoxybeosyl (1S, cis) -4- (Z-2-chloro-3,3,3-trifluoropropyl-11en-1-yl) -2,2 -dioethylcyatoptophoahrbtxyláteo and not more than 10% wt. other isomers of hlaaacyant13-phentxybenzyl cis- (2-chloro-3,3,3-trifluoropropyl-1-en-1-yl) -2,2-dioethylcyclopropanecabotyl. ³